Evidence for a functional beta 3-adrenoceptor in man
- PMID: 7905344
- PMCID: PMC2175798
- DOI: 10.1111/j.1476-5381.1993.tb13902.x
Evidence for a functional beta 3-adrenoceptor in man
Abstract
1. The existence of a functional beta 3-adrenoceptor in man was investigated by studying the lipolytic action of selective beta-adrenoceptor agents in isolated white omental and subcutaneous fat cells. 2. The non-selective beta 1/beta 2-adrenoceptor antagonist, CGP 12177 was lipolytic in both omental and subcutaneous fat cells. The intrinsic activity relative to isoprenaline was greater in omental than in subcutaneous cells. 3. Addition of the beta 2-adrenoceptor antagonist, ICI 118,551 and the beta 1-adrenoceptor antagonist CGP 20712A in combination or the non-selective beta-adrenoceptor antagonist propranolol alone (all 10(-7) M), induced a rightward shift of the dose-response curves for isoprenaline- and BRL37344-stimulated lipolysis of about 4 and 2 log-units, respectively. However, the antagonists did not alter lipolysis induced by CGP12177. 4. Several concentrations of beta-adrenoceptor antagonists were used to determine the pA2 values by Schild analysis. The values for CGP 20712A and ICI 118,551 (6.63 +/- 0.20 and 6.25 +/- 0.12) as antagonists of the lipolytic effects of CGP 12177 were over 2 units lower than the pA2 value for CGP 20712A against the response to the selective beta 1-agonist dobutamine (8.58 +/- 0.23) and the pA2 value for ICI 118,551 against the response to the selective beta 2-agonist terbutaline (9.15 +/- 0.26). 5. beta 3-Adrenoceptor mRNA expression, investigated with a polymerase chain reaction assay, was demonstrated in both types of adipocytes in the same cell preparations that had a lipolytic response to CGP 12177. 6. In conclusion, human white fat cells express an atypical beta-adrenoceptor in addition to beta 1- and beta 2-adrenoceptors. This receptor is stimulated more selectively by the beta1/beta2-antagonist CGP 12177 than by BRL 37344 and is poorly sensitive to blockade by selective beta1- and beta2-antagonists. On the basis of the pharmacological properties and the mRNA analyses, we suggest that this atypical receptor corresponds to the beta 3-adrenoceptor subtype.
Similar articles
-
Human heart beta-adrenoceptors: beta1-adrenoceptor diversification through 'affinity states' and polymorphism.Clin Exp Pharmacol Physiol. 2007 Oct;34(10):1020-8. doi: 10.1111/j.1440-1681.2007.04730.x. Clin Exp Pharmacol Physiol. 2007. PMID: 17714089 Review.
-
Lipolytic effects of conventional beta 3-adrenoceptor agonists and of CGP 12,177 in rat and human fat cells: preliminary pharmacological evidence for a putative beta 4-adrenoceptor.Br J Pharmacol. 1997 Nov;122(6):1244-50. doi: 10.1038/sj.bjp.0701523. Br J Pharmacol. 1997. PMID: 9401793 Free PMC article.
-
Beta-adrenoceptor subtype expression and function in rat white adipocytes.Br J Pharmacol. 1997 Jan;120(2):201-10. doi: 10.1038/sj.bjp.0700885. Br J Pharmacol. 1997. PMID: 9117110 Free PMC article.
-
Determination of beta 3-adrenoceptor mediated lipolysis in human fat cells.Obes Res. 1995 Sep;3(5):447-57. doi: 10.1002/j.1550-8528.1995.tb00174.x. Obes Res. 1995. PMID: 8521164
-
Regulation of beta 3-adrenoceptor expression in white fat cells.Fundam Clin Pharmacol. 1995;9(2):97-106. doi: 10.1111/j.1472-8206.1995.tb00268.x. Fundam Clin Pharmacol. 1995. PMID: 7628838 Review.
Cited by
-
Is the β3-Adrenoceptor a Valid Target for the Treatment of Obesity and/or Type 2 Diabetes?Biomolecules. 2023 Nov 28;13(12):1714. doi: 10.3390/biom13121714. Biomolecules. 2023. PMID: 38136585 Free PMC article. Review.
-
β3-Adrenergic receptors regulate human brown/beige adipocyte lipolysis and thermogenesis.JCI Insight. 2021 Jun 8;6(11):e139160. doi: 10.1172/jci.insight.139160. JCI Insight. 2021. PMID: 34100382 Free PMC article.
-
A compendium of G-protein-coupled receptors and cyclic nucleotide regulation of adipose tissue metabolism and energy expenditure.Clin Sci (Lond). 2020 Mar 13;134(5):473-512. doi: 10.1042/CS20190579. Clin Sci (Lond). 2020. PMID: 32149342 Free PMC article. Review.
-
Agonist-induced desensitisation of β3 -adrenoceptors: Where, when, and how?Br J Pharmacol. 2019 Jul;176(14):2539-2558. doi: 10.1111/bph.14633. Epub 2019 Apr 7. Br J Pharmacol. 2019. PMID: 30809805 Free PMC article. Review.
-
Adrenoceptors in white, brown, and brite adipocytes.Br J Pharmacol. 2019 Jul;176(14):2416-2432. doi: 10.1111/bph.14631. Epub 2019 Apr 7. Br J Pharmacol. 2019. PMID: 30801689 Free PMC article. Review.
References
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases